Emphasis was placed on the estrogenic action of chlorinated hydrocarbons in the rat, primarilyearly biochemical events in estrogen expression. The question of whether methoxychlor and o,p'DDT are proestrogens or estrogens was examined. Our in vitro data indicates that methoxychlor is a proestrogen, since metabolism was needed for binding interaction with the estrogen receptor, whereas o,p'DDT acts as an estrogen since binding to the uterine cytosolic receptor and translocation of the receptor into the nucleus occurs without the necessity for metabolic activation. By contrast in vivo both methoxychlor and o,p'DDT act as typical estroqens increasing uterine weight and elevating uterine ornithine decarboxylase. Similarly Kepone acts both in vivo and in vitro as a typical estroqen.